chr3-3042463-A-G

Variant names:

• chr3-3042463-A-G
• rs163560
• NM_175607.3:c.2511+41A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_175607.3(CNTN4):​c.2511+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,268,916 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4913 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12933 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.67
• Publications: 4 publications found

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4-AS1 (HGNC:39985): (CNTN4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-3042463-A-G is Benign according to our data. Variant chr3-3042463-A-G is described in ClinVar as Benign. ClinVar VariationId is 1177914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	NM_175607.3	MANE Select	c.2511+41A>G		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2511+41A>G		intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2511+41A>G		intron	N/A	NP_001337024.1	Q8IWV2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.2511+41A>G		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1527+41A>G		intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.761+41A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32958 AN: 151940 Hom.: 4898 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.204

GnomAD2 exomes AF: 0.154 AC: 37397 AN: 243620 AF XY: 0.148

Gnomad AFR exome AF: 0.444

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.202

Gnomad FIN exome AF: 0.0957

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.141 AC: 157579 AN: 1116858 Hom.: 12933 Cov.: 15 AF XY: 0.140 AC XY: 79882 AN XY: 572480

African (AFR) AF: 0.436 AC: 11701 AN: 26818

American (AMR) AF: 0.107 AC: 4709 AN: 43808

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 5882 AN: 23916

East Asian (EAS) AF: 0.177 AC: 6736 AN: 38052

South Asian (SAS) AF: 0.110 AC: 8671 AN: 78902

European-Finnish (FIN) AF: 0.0930 AC: 4917 AN: 52870

Middle Eastern (MID) AF: 0.198 AC: 1017 AN: 5138

European-Non Finnish (NFE) AF: 0.133 AC: 106130 AN: 798376

Other (OTH) AF: 0.160 AC: 7816 AN: 48978

GnomAD4 genome AF: 0.217 AC: 33012 AN: 152058 Hom.: 4913 Cov.: 32 AF XY: 0.212 AC XY: 15747 AN XY: 74338

African (AFR) AF: 0.425 AC: 17618 AN: 41406

American (AMR) AF: 0.159 AC: 2436 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3466

East Asian (EAS) AF: 0.185 AC: 959 AN: 5170

South Asian (SAS) AF: 0.112 AC: 537 AN: 4814

European-Finnish (FIN) AF: 0.0948 AC: 1007 AN: 10618

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.134 AC: 9112 AN: 67996

Other (OTH) AF: 0.203 AC: 427 AN: 2106

Alfa AF: 0.166 Hom.: 1970

Bravo AF: 0.233

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.36
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs163560; hg19: chr3-3084147; COSMIC: COSV61876315; COSMIC: COSV61876315;